Two alkylating benzodiazepines, shown earlier to irreversibly inhibit the receptors in vitro have now been shown to afford long lasting antagonism of pentylenetetrazole induced seizures in vivo (mice), probably through covalent binding to the receptors. 3-Hydroxymethyl-beta-carboline has been identified as an antagonist to the anxiolytic and anticonovlsant effects of Diazepam at doses which do not elicit overt behavorial effects. R-(+)-and S-(-)-(1,3-dimethylbutyl)-5-ethylbarbituric acids were synthesized as neuropharmacological research probes, by a route that insured optical purity and demonstrated the absolute configuration. These enantiomers showed a five-fold difference in enhancement of Diazepam binding to the receptors. Electrophysiological examination of these enantiomers is in progress in an attempt to relate electrophysiological action to enhancement of benzodiazepine binding by barbituates.